Breast cancer is the most common form of cancer in women. In the year 2000, it is predicted that approximately 180,000 new cases of breast cancer will be diagnosed in the United States, and 40,000 women will die from the disease. The key to successful treatment of breast cancer is early diagnosis, and the use of widespread mammography screening has resulted in significant improvements in breast cancer survival rates. However, a major problem with mammography is a lack of specificity; 70-80% of suspicious lesions on mammography referred for biopsy ultimately have a benign final diagnosis. These "unnecessary" biopsies represent a significant economic burden on health care systems, and are also invasive and unpleasant for the patient. Therefore, there is a need for the development of new non-invasive, cost-effective, and safe imaging procedures with enhanced specificity and sensitivity. Proton MR spectroscopic imaging (MRSI) is a non-invasive metabolic imaging technique, which has yet to be applied to human breast cancer. Preliminary data from our group and others, based on cell preparations, in vitro studies and single-voxel human spectroscopy, suggest that an elevated composite choline signal (detected in the proton MR spectrum) is a marker of malignant breast disease. Benign lesions and normal breast tissue have little or no detectable choline signal. However, technical developments are required before proton MRSI can become a clinical procedure for evaluating breast cancer. These include maximizing spatial resolution, optimizing water and lipid suppression techniques, development of quantitation methodology, and providing whole breast coverage within a clinically acceptable scan time. We will develop and test these techniques in years one and two of this proposal (phase I, R21), and in years 3 and 4 (phase II, R33) we will apply these techniques to a trial of proton MRSI in human breast cancer. Specifically, choline levels will be compared between histologically defined tissue types, in patients who are scheduled for breast biopsy. The sensitivity and specificity of proton MRSI in this patient group will be determined. The techniques developed in this proposal will also assist in the translation of proton MRSI to other organ systems and pathologies, and increase the acceptance of clinical proton MRSI as a diagnostic imaging modality.